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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
53.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
other: NOAEL
Value:
1 345 mg/m³
Explanation for the modification of the dose descriptor starting point:
Oral repeated dose NOAEL value is chosen as starting point
AF for differences in duration of exposure:
2
Justification:
subchronic oral study NOAEL value of 763 mg/kg/d is used for calculation.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
6 410 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
134.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
other: NOAEL 763 mg/kg/d
AF for differences in duration of exposure:
2
Justification:
subchronic oral study NOAEL value of 763 mg/kg/d is used for calculation.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
381.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
38 150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Oral repeated dose NOAEL value is chosen as starting point
AF for differences in duration of exposure:
2
Justification:
subchronic study NOAEL value of 763 mg/kg/d is used for calculation.
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
2 000 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 630 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
other: NOAEL
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

In general, assessment factors (AF) recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, Version 2.1, November 2012) were used when applicable to derive the DNELs. Several AFs for which there is additional information were refined. The difference in metabolic rate between humans and the test species has been taken into account, where relevant.

Workers- Hazard via inhalation route: Systemic effects, Long-term exposure: Since there is no dose descriptor for inhalation exposure, dose descriptors were converted into a correct starting point by route-to-route extrapolation based on the ECHA guidance document "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", Dec 2010. The conversion of an oral NOAEL into an inhalatory NAEC is performed using the following equations: for workers the resulting concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity;

Corrected inhalatory NOAEC = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-humanx sRVhuman/wRV                                                                                                 = oral NOAEL x 1/0.38m³/kg bw x 1 x 6.7 m³/10 m³

= 763 mg/kg/d x 2.63 x 0.67  

= 1345.3 mg/m3

SRV: standard respiratory volume, ABS: absorption, wRV: worker respiratory volume. For the route-to-route extrapolation (oral to inhalation) the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rats (0.38 m3/kg for 8 hours exposure of workers). The resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity (6.7 m3/worker for basal activity, 10 m3/worker in 8 hours for light activity). [as a worst case assumption: both oral absorption and absorption after inhalation is equal]. The corrected NOAEC was divided by an assessment factor of 25, derived from 2.5, interspecies, remaining differences), 5 (intraspecies, worker) and 2 (exposure duration, subchronic to chronic). The long-term DNEL, inhalation for systemic effects of 53.8 mg/m3 is derived.

Workers- Hazard via dermal route: Systemic effects, Long-term exposure: Although a good quality dermal toxicity study is available, oral NOAEL will be used for the derivation of systemic DNEL.

The conversion of an oral NOAEL into a dermal NAEC is performed using the following equations:

Corrected dermal NAEL = oral NOAEL x ABSoral-rat/ABSdermal                                       

                                      = oral NOAEL x 50/1

ABS: absorption

The oral absorption factor is set to 50%, based on the anticipated hampered diffusion of SDIBP as an ionized substance and low Kow value. Based on state-of-science modeling, a 2.8% dermal absorption factor can be used as an upper bound value in general population exposure dose calculations for hydrotrophes, therefore a default assumption of 1% for all modeled exposures for SDIBP will display a sufficient conservative approach. The worker dermal starting point was a 763 mg/kg bw/day NOAEL in a rat 90 day study with oral exposure. The corrected NOAEL value of 38150 mg/kg bw/day as divided by an assessment factor of 100. The overall assessment factor of 100 was derived combining a factor of 10 (interspecies), 5 (intraspecies, worker) and 2 (exposure duration subchronic to chronic), resulting in a dermal DNEL for workers of 381.5 mg/kg.

 

Acute effects:

Based on the acute toxicity data, DNELs do not need to be derived for acute effects for the worker population since the SDIBP has a low potential for acute toxicity.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.27 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
663.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
Oral repeated dose NOAEL value is chosen as starting point
AF for differences in duration of exposure:
2
Justification:
subchronic study NOAEL value of 763 mg/kg/d is used for calculation.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
6 410 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.17 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor:
other: NOAEL 763 mg/kg/d
AF for differences in duration of exposure:
2
Justification:
subchronic oral study NOAEL value of 763 mg/kg/d is used for calculation
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
190.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
38 150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Oral repeated dose NOAEL value is chosen as starting point
AF for differences in duration of exposure:
2
Justification:
subchronic study NOAEL value of 763 mg/kg/d is used for calculation.
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
2 000 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 815 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.82 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
763 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Oral repeated dose NOAEL value is chosen as starting point
AF for differences in duration of exposure:
2
Justification:
subchronic study NOAEL value of 763 mg/kg/d is used for calculation.
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
2 000 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

In general, assessment factors (AF) recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, Version 2.1, November 2012) were used when applicable to derive the DNELs. Several AFs for which there is additional information were refined. The difference in metabolic rate between humans and the test species has been taken into account, where relevant.

General population- Hazard via inhalation route: Systemic effects, Long-term exposure: Since there is no dose descriptor for inhalation exposure, dose descriptors were converted into a correct starting point by route-to-route extrapolation based on the ECHA guidance document "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", Dec 2010. The conversion of an oral NOAEL into an inhalatory NAEC is performed using the following equations:for consumers the resulting concentration needs to be additionally corrected for the difference between basal caloric demand;

Corrected inhalatory NOAEC = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh

  = 763 mg/kg/d x 1/1.15 m3/kg bw

= 663.4 mg/m3

RV: standard respiratory volume, ABS: absorption For the route-to-route extrapolation (oral to inhalation) the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rats (1.15 m3 / kg for 24 hours exposure of general public).[as a wost case assumption: both oral absorption and absorption after inhalation is equal]. The corrected NOAEC was divided by an assessment factor of 50, derived from 2.5 (interspecies, remaining differences), 10 (intraspecies, consumers) and 2 (exposure duration, subchronic to chronic). The long-term DNEL, inhalation for systemic effects of 13.27 mg/m3 is derived.

General population- Hazard via dermal route: Systemic effects, Long-term exposure: Although a good quality dermal toxicity study is available, for the derivation of systemic DNELs studies with oral exposure will be used.

The conversion of an oral NOAEL into a dermal NAEC is performed using the following equations:

Corrected dermal NAEL = oral NOAEL x ABSoral-rat/ABSdermal                                      

  = oral NOAEL x 50/1

ABS: absorption

The oral absorption factor is set to 50%, based on the anticipated hampered diffusion of SDIBP as an ionized substance and low Kow value. Based on state-of-science modelling, a 2.8% dermal absorption factor can be used as an upper bound value in general population exposure dose calculations for hydrotrophes, therefore a default assumption of 1% for all modelled exposures for SDIBP will display a sufficient conservative approach.The corrected NOAEL value of 38150 mg/kg bw/day was divided by an assessment factor of 200. The overall assessment factor of 200 was derived combining a factor of 10 (interspecies), 10 (intraspecies, consumer) and 2 (exposure duration subchronic to chronic), resulting in a dermal DNEL for consumers of 190.75 mg/kg.

  

General population- Hazard via oral route: Systemic effects, Long-term exposure:

Oral repeated toxicity dose will be used for calculation. The NOAEL value of 763 mg/kg bw/day was divided by an assessment factor of 200 derived combining a factor of 10 (interspecies), 10 (intraspecies, consumer) and 2 (exposure duration subchronic to chronic).

Acute effects:

Based on the acute toxicity data, DNELs do not need to be derived for acute effects for the general population since the SDIBP has a low potential for acute toxicity.